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Lithium‐stimulated proliferation and alteration of phosphoinositide metabolites in MCF‐7 human breast cancer cells
Author(s) -
Welshons Wade V.,
Engler Kathleen S.,
Taylor Julia A.,
Grady Leigh H.,
Curran Edward M.
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041650116
Subject(s) - inositol , lithium (medication) , endocrinology , mcf 7 , lithium chloride , medicine , chemistry , cell growth , cancer cell , biology , biochemistry , cancer , receptor , human breast , organic chemistry
Lithium, which is used to treat bipolar psychiatric disorders, can stimulate proliferation of a number of cells in tissue culture. Proliferation of MCF‐7 human breast cancer cells, which also respond to EGF and estrogens, was stimulated by LiCl (1–5 mM) within the concentration range that is encountered during human therapy with lithium. Stimulation of growth was specific for lithium; rubidium, potassium, and sodium showed no such effect. In the presence of antiestrogen, lithium stimulated the growth of hormone‐dependent breast cancer cells MCF‐7, ZR‐75‐1, and T47D but not hormone‐independent MDA‐MB‐231 cells or an estrogen‐independent clone of MCF‐7 cells. Lithium‐stimulated proliferation was limited by cytotoxicity which could be moderated by added potassium chloride (5–20 mM) in the medium. Each of the mitogens lithium, 17β‐estradiol, and EGF increased the rate of uptake of myo ‐inositol into MCF‐7 cells. Whether normalized to inositol lipids, to protein, or to DNA, steady‐state levels of inositol phosphates were elevated by each of the mitogens including lithium, which inhibits the breakdown of inositol phosphates in the phosphoinositide signaling pathway. These data indicate that therapeutic concentrations of lithium can stimulate the proliferation of human breast cancer cells by a mechanism that may involve the phosphoinositide pathway. © 1995 Wiley‐Liss Inc.